Treatment plan robustness in pancreatic patients treated with scanned ion-beam therapy: Inter- and intra-fractional aspects

Pancreatic cancer is still an unsolved oncological challenge, however radiotherapy with charged particles has been considered a promising approach to improve the patients overall survival. These patients might benefit from dose escalation, although uncertainties during the beam delivery (intra-fractional) or along the treatment course (inter-fractional) can compromise the accuracy of the treatment. In this thesis, inter- and intra-fractional anatomy changes are explored in order to define the potential source of uncertainties, quantify their effect, and to define strategies towards their reduction. Anatomical changes along the course of the treatment showed to lead target under-dosages up to 20% and an increase in the dose to the normal tissues. However, this can be lowered through the selection of beam arrangements from the patient's posterior side and beam-specific margins. From the results of this work, it was concluded that a combination of an Internal Target Volume (ITV), obtained by a geometric expansion of 3 mm from the Clinical Target Volume (CTV), and two oblique posterior beams can reduce the mean V95CTV variations to less than 1%. For other beam directions, the calculation of ITVs including the water-equivalent path length (WEPL), suggested the need for a CTV asymmetric expansion in depth, and minimal in lateral beam direction. Additionally, weekly monitoring of the patient anatomy using computed tomography (CT) might easily be included in the clinical workflow and will assist in the decision of treatment re-planning, when substantial anatomical changes occur. The suggested prediction model was based on the variations of the accumulated WEPL (∆accWEPL) relative to the planning CT, and showed a strong correlation between the ∆accWEPL and the gamma index of the dose distributions. The gamma criterion was selected as dose distribution quality metric, since it includes dosimetric changes in the target and normal tissues. Regarding intra-fractional variations, the induced breathing motion together with a dynamic beam delivery, affect the dose distribution in terms of homogeneity and target coverage. This effect is stronger (∆V95CTV > 10%) for patients with a tumor motion amplitude superior to 5 mm and a highly modulated dose distribution intra- and inter-fields. The concept of modulation index was employed, it showed that different optimisers produce plans with contrasting distribution of the number of particles, resulting in unlike robustness against range and positioning uncertainties. It was concluded that under internal motion, the use of homogeneous plans, multiple beams, and geometric ITVs, originated dose distributions exhibiting a slight mean decrease of the dose homogeneity (H_CTV) and V95CTV of 4% and 1%, respectively. Finally, a first approach to the use of 4D-Magnetic Resonance Imaging (MRI) for motion detection was performed. The results revealed cases of non-linear correlation between the breathing signal (diaphragm position) and the pancreas motion, and variability of the motion amplitude along the acquisition time and between sessions. This reinforces the need of an alternative method, comparative to the use of external surrogates, for simulation of a 4D dose distribution. Therefore, MRI will allow to include baseline drifts, amplitude variations and anatomical alterations in the 4D dose distribution assessment. In summary, the key for a precise delivery of the treatment is the monitoring of anatomical changes, and a prompt reaction in order to minimise or eliminate potential uncertainties. In future, it is expected that the methods suggested in this thesis, the experience gained at HIT on treating moving organs and, the developments in treatment planning and treatment delivery will allow us to move towards the robust plan optimisation, prediction of changes in the dose distribution, and enable treatment without a constant and complex monitoring of the patient's movement

Planning strategies for inter-fractional robustness in pancreatic patients treated with scanned carbon therapy

Background: Managing inter-fractional anatomy changes is a challenging task in radiotherapy of pancreatic tumors, especially in scanned carbon-ion delivery. This treatment planning study aims to focus on clinically feasible solutions, such as the beam angle selection and margin design to increase the robustness against inter-fractional uncertainties. Methods: This study included 10 patients with weekly 3D-CT imaging and physician-approved Clinical Target Volume (CTV). The study was directed to keep the CTV-coverage using six beam angle configurations in combination with different Internal Target Volume (ITV) concepts. These were: geometric-margin (symmetric 3 and 5 mm margin); range-equivalent margins with an isotropic HU replacement; and to evaluate the need of asymmetric margins the water-equivalent range path (WEPL) was determined per patient from the set of CTs. Plan optimization and forward dose calculation in each week-CT were performed with the research treatment planning system TRiP98 and the plan quality evaluated in terms of CTV coverage (V95CTV) and homogeneity dose (HCTV = D5-D95). Results: The beam geometry had a substantial impact on the target irradiation over the treatment course, with the single posterior or two beams showing the best average coverage of the CTV. The use of geometric margins for the more robust beam geometries showed acceptable results, with a V95CTV of (99.2 ± 1.2)% for the 5 mm-margin. For the non-robust configurations, due to substantial changes in the radiological depth, the use of this margin results in a V95CTV that might be below 80%, only showing improvement when the range changes are included. Conclusions: Selection of adequate beam configurations and treatment margins in ion-beam therapy of pancreatic tumors is of great importance. For a single posterior beam or two beam configurations, application of geometrical margins compensate for dose degradation induced by inter-fractional anatomy changes for the majority of the analyzed treatment fractions

Significance of intra-fractional motion for pancreatic patients treated with charged particles

Background; Uncertainties associated with the delivery of treatment to moving organs might compromise the accuracy of treatment. This study explores the impact of intra-fractional anatomical changes in pancreatic patients treated with charged particles delivered using a scanning beam. The aim of this paper is to define the potential source of uncertainties, quantify their effect, and to define clinically feasible strategies to reduce them. Methods: The study included 14 patients treated at our facility with charged particles (protons or 12C) using intensity modulated particle therapy (IMPT). Treatment plans were optimized using the Treatment Planning System (TPS) Syngo® RT Planning. The pre-treatment dose distribution under motion (4D) was simulated using the TPS TRiP4D and the dose delivered for some of the treatment fractions was reconstructed. The volume receiving at least 95% of the prescribed dose (V95CTV) and the target dose homogeneity were evaluated. The results from the 4D dose calculations were compared with dose distributions in the static case and its variation correlated with the internal motion amplitude and plan modulation, through the Pearson correlation coefficient, as well the significant p-value. The concept of the modulation index (MI) was introduced to assess the degree of modulation of IMPT plans, through the quantification of intensity gradients between neighboring pencil beams. Results: The induced breathing motion together with dynamic beam delivery results in an interplay effect, which affects the homogeneity and target coverage of the dose distribution. This effect is stronger (∆V95CTV > 10%) for patients with tumor motion amplitude above 5 mm and a highly modulated dose distribution between and within fields. The MI combined with the internal motion amplitude is shown to correlate with the target dose degradation and a lack of plan robustness against range and positioning uncertainties. Conclusions: Under internal motion the use of inhomogeneous plans results in a decrease in the dose homogeneity and target coverage of dose distributions in comparison to the static case. Plan robustness can be improved by using multiple beams and avoiding beam entrance directions susceptible to density changes. 4D dose calculations support the selection of the most suitable plan for the specific patient’s anatomy

A metoclopramida prejudica a cicatrização de anastomoses do cólon esquerdo de ratos?

Objetivo: Avaliar os efeitos da metoclopramida sobre a formação de aderências e a cicatrização de anastomoses de cólon esquerdo de ratos. Métodos: 40 ratos distribuídos em dois grupos contendo 20 animais, para administração de metoclopramida (grupo experimental - E) ou solução de NaCl 0,9% (grupo controle - C). Cada grupo foi dividido em subgrupos contendo 10 animais, para eutanásia no terceiro (E3 e C3) ou sétimo dia (E7 e C7) de pós-operatório. Os ratos foram submetidos à secção do cólon esquerdo e anastomose término-terminal. No dia da relaparotomia foi avaliada a quantidade total de aderências e removido um segmento colônico contendo a anastomose para análise da força de ruptura e concentração de hidroxiprolina. Resultados: Não houve mortes ou deiscências no 3° dia de pós-operatório. No grupo E7 ocorreram uma morte e uma deiscência de anastomose bloqueada. Não houve diferença significativa entre os grupos em relação à evolução clínica, quantidade de aderências intra-cavitárias ou à anastomose e resistência tênsil no 3° ou 7° pós-operatório. A concentração de hidroxiprolina foi maior no grupo metoclopramida no 3° (p=0,006) mas não no 7° dia de pósoperatório (p=0,241) Conclusão: A metoclopramida não apresenta efeito deletério sobre a cicatrização de anastomoses intestinais em ratos. _________________________________________________________________________________ ABSTRACTPurpose: To evaluate the effects of metoclopramide on the formation of adhesion and the healing of left colonic anastomoses in rats. Methods: Forty rats underwent sectioning of the left colon and end-to-end anastomosis and were divided into two groups of 20 animals for the administration of metoclopramide (experimental group - E) or saline solution (control group - C). Each group was divided into subgroups of 10 animals each to be killed on the third (E3 and C3) or seventh postoperative day (E7 and C7). Adhesion was assessed, and a colonic segment containing the anastomosis was removed for analysis of breaking strength and hydroxyproline concentration. Results: There were no deaths or dehiscence on the 3rd postoperative day. There was one death and one blocked anastomotic dehiscence in the E7 group. No significant differences between groups were found in the analysis of clinical outcome, intra-cavity adhesion, adhesion to the anastomosis or breaking strength on the 3rd and 7th postoperative day. Hydroxyproline concentration was higher in the control group on the 3rd (p=0.006) but not on the 7th postoperative day (p=0.241). Conclusion: Metoclopramide did not have harmful effects on the healing of intestinal anastomoses in rats

Análise fundamentada de uma oficina de trigonometria: as contribuições para o desenvolvimento profissional

A partir de uma oficina destinada a alunos do ensino médio, que visava oportunizar a visualização dos padrões existentes entre os ângulos e arcos da circunferência trigonométrica e sua relação com os valores do seno, cosseno e tangente, com o uso de materiais manipuláveis e recursos visuais, este estudo teve o objetivo de compreender as possíveis contribuições do planejamento, do desenvolvimento e da reflexão dessa oficina para o desenvolvimento profissional de um grupo de professoras. Nessa prática, estiveram envolvidas uma professora formadora, que atua na educação básica e na licenciatura em matemática, e duas futuras professoras de matemática. Trata-se de um relato de experiência que, utilizou-se dos materiais disponibilizados pela professora responsável e de uma roda de conversa com todas as envolvidas. Observou-se que a oficina contribuiu para a formação das futuras professoras, no sentido de envolvê-las com os conhecimentos da didática da matemática, evidenciados em seus relatos e notabilizados, posteriormente, pela busca da formação continuada. Em relação à professora responsável, nota-se que, a partir da referida oficina, a docente também buscou a formação continuada e passou a destinar maior atenção ao planejamento de suas aulas

Learning opportunities experienced by mathematics teachers: unveiling actions and role of the teacher educator during a formative process

Context: One of the research challenges related at the professional learning of mathematics teachers is to understand the importance of the role and actions of the teacher educator during a formative process. Objective: This research seeks to understand what the role was and how the actions of the teacher educator took place, in a process of continuing education with teachers of basic education, about the teaching of patterns and regularities, with a view to providing learning opportunities to the teachers involved. Design: It is a qualitative-interpretative study aligned to an intervention research. Settings and Participants: We developed the research in a formative process involving 33 mathematics teachers and future teachers, and 3 teacher educators. Data collection: We use data from audio and video recordings of planning and enacting of the formative process, and protocols from teachers’ tasks and planning from teacher educators. Results: We found that teacher educators, since planning the formative process, sought to provide opportunities for participating teachers professional learning, since he/she structured the process through professional learning tasks, using videos of mathematics lessons to highlight the classroom practice, as well as encourage discussions among teachers about patterns and regularities in and for the teaching of algebra. Conclusions: We identified that teacher educators played a mediating role in the orchestration of the discussions and an articulator between mathematics and didactics, thus providing opportunities for professional development and the learning of teaching algebra

QUALIDADE MICROBIOLÓGICA E FÍSICO-QUÍMICA DE QUEIJO MINAS FRESCAL ARTESANAL E INDUSTRIAL

A produção de queijos é uma forma apropriada de conservar o leite, transformando-o em produto mais estável, cujas qualidades são mantidas. No comércio são encontrados queijos Minas frescal nas comercializados industrial e artesanal, e fazem parte da tradição alimentar de todo país, atingindo todas as classes sociais. O presente trabalho avaliou as características físico-químicas, analisou a rotulagem e verificou as condições higiênico sanitárias quanto presença de Salmonella spp; contagem de Staphylococcus aureus, de coliformes termotolerantes e totais de queijos Minas frescal, produzidos industrialmente e artesanalmente na região Sul do estado de Goiás. Foram utilizadas 5 amostras de queijos industrializados, 5 de queijos artesanais comercializados em supermercados. Os resultados revelaram que grande parte das amostras estavam em desacordo com a legislação, quanto a contagem de coliformes totais e termotolerantes apresentando valores superiores a 1100 NMP/g., e a presença de Staphylococcus aureus, havendo ausência de Salmonella spp. Para as análises físico-químicas, os resultados demostraram estar de acordo com a legislação vigente. Quanto à avaliação da conformidade de rotulagem das embalagens, constatou-se que 90% das amostras industrializadas estavam em acordo com a legislação em vigor e 100% das artesanais estavam em desacordo. Assim determina-se que de acordo com a legislação vigente os queijos estavam em não conformidade, constatando possíveis falhas no controle da qualidade no processamento e armazenamento dos queijo

Webgd Acessível – uma Proposta de Interface

O presente artigo tem como objetivo apresentar a interface desenvolvida para o Ambiente Virtual de Ensino Aprendizagem “WebGD Acessível”, que tem como objetivo servir como suporte didático no processo de aprendizagem na área de representação gráfica espacial, tanto paes usuários sem deficiência quanto para àqueles usuários que tem algum tipo de deficiência visual ou auditiva. Após estudo teórico, partiu-se para uma pesquisa aplicada para o desenvolvimento da interface. Como resultado, a interface disponibiliza recursos,como por exemplo, área para interpretação de LIBRAS para usuários com deficiência auditiva;uso de cores adequadas aos que possuem baixa visão, adequação para leitores de tela. Esses recursos combinados ou não auxiliam os usuários em uma melhor apreensão das informações